1. Technical Field
The present invention relates to a new type of bioactive composition which can be used in a prophylactic or reconstructive manner by preserving substantially sound mineralized tissue as well as for promoting remineralization of minerally defective skeletal tissue, such as teeth and bones. More particularly, the present invention is directed to compositions containing amorphous calcium phosphate and unsaturated monomers and to the hardened polymeric composites which they form. The present invention is also directed to a method of treating teeth and bones to effect mineralization.
2. Discussion of Related Art
Over the years, various materials have been used to treat, fill or alter skeletal tissue or to adhere a prosthetic device thereto. Thus, in the fields of orthopedics and dentistry, materials have been used and sought which seal or fill cracks or caries in bones or teeth and which provide support, strength and resistance to deterioration due to the environment found in the particular portion of the body in which they are used. Such materials have included various kinds of metals including alloys and amalgams, inorganic compositions, including ceramic materials, as well as plastic materials, including organic polymers. While many of these materials have been fairly effective in providing several of the desirable properties such as affinity for living tissue, for example skeletal tissue, and possibly foreign materials; mechanical strength; inertness to the biological environment in which they are placed; storage stability; and ease of manipulation, many lack one or more of these desirable properties. In addition, some of these materials cause damage to adjacent tissue, by erosion or the like, at or subsequent to the time when they are introduced to the body or demonstrate unacceptable levels of toxicity.
It has been realized that those materials which are closest to skeletal tissue both chemically and structurally, are least likely to demonstrate the aforementioned problems. Furthermore, where the materials are sufficiently similar in structure and chemical properties to the skeletal tissue, the body perceives little difference in chemical characteristics, performance or function at the affected site.
The high concentrations of inorganic substances distinguish skeletal tissue such as teeth and bones, from other types of tissue. In vertebrates, skeletal tissue is characterized by high concentrations of calcium and phosphate ions with lower proportions of sodium, magnesium, carbonate and fluoride ions. Characteristics of hardness and rigidity are attributable in skeletal tissue to these inorganic components, largely formed as crystalline salts. Although the mineral-material found in skeletal tissue as well as the chemical pathway to its formation appears to be complex, the predominant chemical structure most closely resembles that of the geomineral, hydroxyapatite (HAP), frequently also referred to as apatite. Although the mechanism by which HAP is formed in biological systems is still not fully understood, it is generally considered to have the formula Ca.sub.5 OH(PO.sub.4).sub.3.
In the field of dentistry, a number-of inorganic and organic materials have been used over the years to adhere prosthetic devices to existing teeth. One such material which combines both organic and inorganic substances with the object of providing compatibility with living tissue, good adhesive properties and high compressive strength, has been described by Adachi (U.S. Pat. No. 4,684,673). The composition which is reported to provide these properties includes amorphous tricalcium phosphate, water and a water-soluble poly(carboxylic acid). After mixing, the amorphous tricalcium phosphate reacts with the carboxylic acid groups in the polymer to set. Such a composition, while somewhat useful not only as a cement but also as a filling material for defective bones and teeth, as well as being useful as a root canal filling material, appears to require a long setting time. Furthermore, as indicated above, while amorphous calcium phosphate can be used in a mineralizing treatment (also referred to as a "remineralizing" treatment when used in reconstruction at sites where skeletal tissue has been eroded), achieving the desired result is somewhat ineffective since a portion of the calcium ions originally present as calcium phosphate are depleted in the reaction with the carboxylic acid groups.
Tung (U.S. Pat. No. 5,037,639) describes a method and composition for mineralizing teeth, particularly to prevent and/or repair dental deficiencies such as dental caries, exposed roots and dentin sensitivity. The method employs amorphous calcium phosphate (ACP), amorphous calcium phosphate fluoride (ACPF) and amorphous calcium carbonate phosphate (ACCP). ACP, which appears to lack crystalline features, has an apparent compositional formula of Ca.sub.3 (PO.sub.4).sub.1.87 (HPO.sub.4).sub.0.2 and exhibits a stoichiometry between that of dicalcium hydrogen phosphate and tricalcium phosphate. In the remineralizing process described, the method involves a short application of the aforementioned amorphous compounds or solutions thereof by contacting the dental tissue with a carrier, such as a solution, gel, chewing gum or toothpaste containing a mineralizing agent. While such compositions include materials suitable for mineralization, in applications involving solutions, either purely aqueous or where the carrier includes or is in the environment of water, such as in the gel, gum or toothpaste, temperature and, more importantly, pH, must be carefully controlled. In addition, since in most instances the duration of the treatment and contact by the mineralization site with the mineralizing composition is so brief, the procedure needs to be repeated several times. In addition, for certain types of treatment, by their nature, require the treatment to be performed by a dentist or dental technician. Furthermore, as with other crystalline materials, greater mechanical strength is provided by larger crystals. Slow growth over a long and continuous period of time favors larger crystal size, a characteristic of which is increased strength. Hence, while such a mineralization method achieves some of the objects of reducing the need for filling of teeth and providing mineralization compositions and methods, the short term direct applications of such compositions to the teeth do not favor the higher degree of strength and structure identified with HAP that occurs naturally in skeletal tissue.